The last month has witnessed several major Fatty Liver conferences and others that touch on NAFLD in the context of metabolic disease. One common theme has been the need for different specialties to align in treating the complete range of non-communicable metabolic diseases. In this episode, Roger Green, Jörn Schattenberg and Louise Campbell propose factors that have the potential to dramatically shift the force around fatty liver disease over the next six months.Jörn starts the conversation with a personal example of a larger trend: he attended last month's EASD meeting for the first time. Historically, few hepatologists attend this meeting, but Jörn believes his attendance is indicative of a trend: hepatologists and endocrinologists working together on diabetes and NAFLD. Louise echoes the sentiment that liver health is gaining traction as a critical function of holistic patient management, although cardiology appears to be slow on the uptake.Roger links this collaborative energy to a completely different kind of energy formation: capital investment. He notes Akero's recent filing for $230 million in equity to help bring efruifermin to market based on Phase 2b results. If this effort succeeds, Roger suggests that it may signify that the financial markets are becoming more optimistic about NASH drugs after several years of extreme skepticism.Next, Jörn returns to his original theme to discuss how endocrinologists have received the concept of liver disease as part of multimorbidity management in patients living with T2DM. He reports that endocrinologists have been enthusiastic about the idea and eager to learn the liver testing tools and metrics they should use.The group then responds to the AACE guidelines promoted last May. The guidelines recommend that front-line physicians not screen their T2DM patients for NAFLD, since 80+% will test positive. Instead, guidelines recommend using a FIB-4 test to identify patients at risk due to current fibrosis. Roger asks whether these will move into actual practice. Louise and Jörn each state that in their countries, front-line treaters are not required to perform liver enzyme blood work. These tests are pivotal for early liver screening. Louise doubts that change will come until after an expensive drug is approved, at which point there will be economic motivation to test. Jörn is more hopeful that with simple tests, he and other hepatologists can educate endocrinologist colleagues on the reasons to adopt this testing strategy over time.The conversation shifts to speculation as to whether prescribers or payers will be the source of bottleneck in patient care pathways at the outset of a drug approval. The group generally agrees that pushback will come from the payers and that healthcare systems are not yet ready. They then look towards the social and political will to take action on the crisis. In response to Roger's question, the group acknowledges the immense hurdles present in changing provider behavior over the next 6-12 months while stressing the importance of provider education and patient empowerment.Finally, the group discusses the future of the recently coined “combo-combo world,” where correct diagnosis will require a combination of biomarker tests and treatment may require a combination of therapies. At the end, Roger asks what changes each member envisions. Surf on to find out.
The 2022 NAFLD Summit presented a range of perspectives and insights on fatty liver and metabolic diseases. Program speakers Mazen Noureddin, Sven Francque and Hannes Hagström join Roger Green on-site from Dublin to review their reactions immediately after the conference ended. In this conversation, the panelists examine the impact of weight change and lifestyle modification in clinical trials while utilizing insights from the bariatric and diabetes fields.This conversation continues the issue of Hawthorne effects in trial design. Hannes starts by noting we can learn from obesity trials – and also from TV shows like “Biggest Loser” – that people regain weight without continued support. Roger shares a thought he believes might have come from absent co-host Louise Campbell, recalling the immediate impact FibroScan has on illustrating results and influencing patient motivation. Sven notes that the issue of lifestyle management in a NASH trial has been a significant issue for the Liver Forum and other supportive groups in terms of trial design and also the power calculations that shape trial size. Mazen closes the discussion by stating that recent meta-analyses show that placebo rates tend to run around 20% and that this might be the right placebo result for power calculations. As the conversation winds down, he shares his guiding principle for these issues: “Prepare for the worst and hope for the best.”This episode is sponsored by Resoundant, a Mayo Clinic company and the developers of Magnetic Resonance Elastography. MRE is widely available with over 2000 locations worldwide, and can be done as a low-cost, rapid exam in just 5 minutes. Together with PDFF, this quantitative exam is called an Hepatogram – a powerful non-invasive alternative to liver biopsy in many cases. For more information, visit www.resoundant.com on the web.
In Season 3, Episode 19, the content focus looks at what the retrospective analysis from the NAIL-NIT consortium can achieve in terms of moving the shift beyond the biopsy in NASH diagnostics forward.This conversation starts with Stephen discussing how challenging it was to develop initial FDA test criteria for evaluating NASH drugs. Many years later, he notes, we have learned how flawed these criteria were, several in ways we cannot fix, but we need to do better. He relates this to what the British author Rupert Sheldrake describes as “morphic resonance” or mysterious telepathy type interconnections between organisms and collective memories within species. One thing leading hepatologists have learned is that you can look at a liver or liver data and get a clear since you are looking at NASH, but it is harder to generate and vet consistently clear data on this point. He points to the REGENERATE trial as a place where specific data analysis did not reflect the gestalt impression and says, “that is what we need to get beyond.”Louise Campbell interjects a very different kind of question, asking whether the NAL-NIT analyses can include questions that patients answer on initial screening in pursuit of AI-driven analyses of these questions to screen patients into or out of further tests..an idea that draws an immediate, enthusiastic response from Naim Alkhouri. In the end, the discussion turns light-hearted and focuses on how many papers the panelists will have to produce in the first year of the program.
The importance of integrating the NAFLD and NASH field within a wider scope of metabolic health was emphasized at the 8th Paris NASH Meeting. Last week, Surfers Roger Green, Louise Campbell and Jörn Schattenberg were in attendance alongside patient advocate and episode guest, Jeff McIntyre.The conversation starts with Roger asking the group about one thing each found particularly striking from the meeting. Jörn responds first, noting his many appearances across the history of the event. He thinks this year's dominating theme to be the engagement of regulatory questions that address moving beyond biopsies and conditional drug approval. Jeff joins to echo this takeaway, adding that he is intrigued by the multinational dynamics of the meeting. Next, Louise recalls a more specific crux. In response to an industry roundtable, she suggests that with the wealth of data provided from clinical trials it is now time to consider changing endpoints. Lastly, Roger offers his general thoughts on witnessing the shifting tensions between the scientific and patient advocate positions and the regulatory and payer responses. The group then compares the American and European positions on moving the field toward a more metabolic perspective. They consider where this pressure comes from in terms of regulators, patients, payers, politicians and employers.Moving on, Roger asks the group for an example of one particular talk or panel that grabbed their imagination and why. Louise returns to the statistics surrounding NASH. She reminds that while the field searches for more data, an expected rise of 110-125% in advanced liver disease and mortality by 2040 is underway. Given the influence of obesity on this rise, Louise highlights the role of allied health professionals in providing lifestyle guidance to mitigate disease progression from an earlier stage.In the closing session, both Jörn and Jeff reflect on participating in discussions surrounding the role of the patient voice and developing a global strategy for NASH. This leads the group to explore the potential for public advocacy in the field of NAFLD and NASH. Afterwards, Roger brings focus to educating physicians and other healthcare professionals on the nature of metabolic disease. By developing an understanding of the multifaceted application of many drugs in a metabolic context, the wait for an F1 or NAFLD drug approval can be possibly eliminated altogether. Louise adds that a pivot is required to move away from organ-centric thinking.Next, the group provides their thoughts on Session 5, starting with response adaptive trial design to pick the best dose. Roger and Jörn share ideas on clinical trial criteria and the use of Bayesian priors in enrichment strategies. Jeff also revisits the role of patient involvement in this topic.Roger then suggests the four go through and connect missing dots between sessions covered in the conversation thus far. After that, the final response:Louise looks toward a bright future with metabolic coordination. She believes patients are key in developing person-centric approaches. Jörn believes that addressing multiple organ systems is the way forward and that it is necessary to partner with other disciplines. Jeff feels grateful for his participation as a patient advocate. He says he is looking for the experience of the science, which in the end feels positive to him. Roger reiterates the importance of investigating these discussions as Paris NASH does. “One thing that became clearer to me in this meeting than it's ever been before, is that this is all about metabolic disease.” He is hopeful. Surf on for the full review.
In this conversation, Roger Green, Louise Campbell, Jörn Schattenberg and Rachel Zayas share their particular interests in what's to come from the 6 sessions hosted at this year's Paris NASH Meeting.Rachel identifies a presentation in Session 2: Clinical Aspects, titled Controversy: are HIV infected patients more at risk of NASH? She notes the specific challenges faced by HIV patients and shares her hope the prompt leads to speculation on how to improve patient stratification. Rachel also brings forth a concept of moving beyond ideas of personalized medicine to what she describes as a more “intentional approach.”Staying in Session 2, Jörn draws anticipation toward a talk by Cyrielle Caussy titled, Type 2 diabetes sub-populations with varying outcome profiles. He is curious to learn something about which type two diabetes patients are more severely liver diseased. Jörn also mentions an interest in the last remaining presentation in Session 2, with Kris Kowdley discussing the natural history and clinical outcomes in adults with NAFLD - lessons from cohort studies and placebo arms of trials.Next, Louise calls attention to the opening session and her interest in the integration of the liver under cardiometabolic health. This topic will be presented by Faiez Zannad. Additionally, Louise mentions NASH PASS. In Session 5, Marcus Hompesch discusses three years of data & experiences on a metabolic disease focused patient registry and biobank supporting biomarker and drug development research.Also in Session 5, Frank Anania of the FDA presents on a subject recently explored in last week's episode 43: How to approach combination therapies for NASH. Following, Roy Sabo discusses response adaptive trial design to pick the best dose. This piques Roger's interest.The tone of this conversation conveys a sense of excitement about what this meeting will bring.
The group concludes the preview of the upcoming Paris NASH conference after taking a thorough look at the diversity of topics in Session 5. Roger Green poses the closing question: What insights or energy would you like to see come out of this event? What is the immediate response, and what's going to stick after 3 to 5 years?Jörn Schattenberg indicates his interest in the future of drug development and what implications this meeting will have on it. In a more immediate sense, he notes an interest in the more recent learnings of disease biology covered in Scott Friedman's basic science sessions.Louise Campbell anticipates an immediate integrated response as a result from this meeting. She suggests a joint meeting between specialists to tease out the implications of liver health in a holistic outcome. “We don't try and repair a car without opening the bonnet to look at the engine - but we're trying to solve diabetes, cardiovascular disease and all of the other linked metabolic diseases without taking the lid off the liver.”Rachel Zayas looks for a joint response across specialities to activate steps to break down thinking in terms of “organ silos.”Roger provides his final thoughts by way of a double entendre on the word “global.”. Global refers to how widely NAFLD-associated challenges vary in different parts of the world, but it also refers to the liver as part of a holistic web of non-communicable metabolic diseases. He concludes, “We need to understand how we're going to address this in different parts of the world, but as the challenges vary, we also need to understand how we're going to address the whole body in the context of the liver.”
The 8th Paris NASH Meeting takes place on September 8th & 9th, where key opinion leaders from both sides of the Atlantic come together to present pivotal learnings and host exciting discussions on fatty liver diseases. Surfers Roger Green, Louise Campbell, and Jörn Schattenberg are joined by Rachel Zayas to discuss this year's program and provide preview commentary on talks and sessions of interest.Roger opens the floor by asking everyone to highlight what specifically stands out to them on the program to look forward to. “Brave one go first.”Rachel notes a presentation in Session 2: Clinical Aspects, titled Controversy: are HIV infected patients more at risk of NASH? Emerging data and insights will be discussed as to why the prevalence of NAFLD, NASH and subsequently fibrosis present higher in HIV-infected patients in comparison to the general population. Rachel hopes the prompt leads to speculation on how to improve patient stratification. She suggests the field is moving beyond ideas of personalized medicine to what is described as a more intentional approach. Jörn echoes Rachel's interest in this topic. There is the need to address not only individuals, but also a group of overlooked patients that call for an intentional and stratified investigation into potentially shared biomarkers. Session 2 also features a discussion on type 2 diabetes sub-populations with varying outcome profiles, solidifying the Clinical Aspects leg as a ‘can't miss' for the whole group.Next, Louise calls attention to the opening session and her interest in the integration of the liver under cardiometabolic health. “That's where we're going to find the breadth and depth of patients for future NASH studies.” She asserts that a larger recruitment to clinical trials will be required in the next 3 to 5 years to move the field forward.Roger relates the relevance of last week's episode on finding the right combinations for NASH therapy. Friday afternoon features a look into the current status and future directions in NIT-based drug development and clinical management of NASH.The conversation shifts to comparative outcomes of the Barcelona meeting and its focus on pathways before transitioning into part 2 of this episode: a one on one interview with Prof. Jeff Lazarus. Much of Jeff's summer was spent working in preparation for the impact COVID will have on the northern hemisphere this autumn. However, he also managed to attend the NAFLD Nomenclature Conference in Chicago. The conference is described as a midway point for a Delphi process that explores the prospect of assigning a new name(s) in the description of fatty liver diseases. What was determined is that should a name change occur, it needs to be organized through global consensus and consistent with the following 6 principles:AffirmativeAccurateAdaptableAdoptableApplicableAbleRoger believes that the meeting was successful at strengthening consensus on this topic. He then asks Jeff to describe his role in the NAFLD Summit and to mention any other presentations of interest outside of his own. Jeff shares that he will be talking about evolving models of care and future implications. Specifically, he is also interested in attending discussions and panels around the impact of NITs in addition to the topic of personalized medicine. Likewise, Roger expresses an interest in emerging technologies before offering a final question - or, rather, a request for commitment. Will Jeff return to the podcast to disclose what occurred at the Wilton Park meeting this October? It seems he might, after a few weeks digestion. Stay tuned, stay safe and surf on.
This conversation from The Vault - Season 3, Episode 25.3 is part of a broader overview of NASH drug development in 2022, led by Stephen Harrison and Jörn Schattenberg. It starts with Louise Campbell asking whether design and management of the ongoing trials will provide sufficient granularity on matching patient types to medications or drug classes. Stephen Harrison notes that we have not paid sufficient attention to this issue historically. In fact, he notes a range of key variables we do not explore at baseline: genotype disease markers like PNPLA3, microbiome and non-Caucasian population segments, to name three. He also notes that some promising drugs have been killed because of trial design issues. In the end, he returns to core positive concepts: combination therapies, looking for agents with multiple positive metabolic effects and safety.At this point in the conversation, Stephen's transmission starts to fail. Eventually, he leaves the conversation and focus shifts to cirrhosis.This episode from the Vault is sponsored by Madrigal Pharmaceuticals.
Louise Campbell convenes liver nursing and nurse educator experts Kathryn Jack, Michele Clayton, Pam O'Donoghue and Patrizia Kunzler to consider where liver nurses and advanced nursing practitioners should fit into treatment and communication paradigms and what support they will need. Stephen Harrison joined to offer a different viewpoint.This conversation explores the need for and value of patient education in the NASH Patient Care process. It starts with almost a tangential request that some of the money budgeted for expensive systemic HCC therapies in the UK be rededicated to patient education earlier in the treatment process.From there, the conversation shifts to consider the value of the need for early-stage treatment strategies in poorer countries that are never likely to be able to afford the expense of drugs or treatment modalities. In the end, each panelist describes a change she would like to see in the next 2-3 years.
THE NASH Tsunami audience came to know Jörn Schattenberg in the Fall of 2020 when he shared a paper he had recently co-authored on why NASH drug trials failed. This week, the same group that discussed that paper – Jörn, Stephen Harrison, Louise Campbell and Roger Green – reflect on what has improved in the intervening time period and what has not. The group speculates what can still be accomplished. This conversation begins with Roger suggesting that tertiary care research universities that have their own primary practice be utilized as an accessible point of referral. The group agrees that while a good idea, this may not translate to the European system.Roger poses the closing question: what is there to look forward to in the space of NASH clinical trials and improving screen fail rates in the next 6 months to a year? Louise is looking for the approval of FibroScan for primary care in the UK. Jörn is hoping for an opportunity to offer health care services through referral systems. Stephen talks about getting a drug approved. In response to the latter, Roger finishes with a Stephen quote: is the juice worth the squeeze? This "juice" takes forms of cash and optimism, and it will be worth the squeeze if a drug sees successful development.
THE NASH Tsunami audience came to know Jörn Schattenberg in the Fall of 2020 when he shared a paper he had recently co-authored on why NASH drug trials failed. This week, the same group that discussed that paper – Jörn, Stephen Harrison, Louise Campbell and Roger Green – reflect on what has improved in the intervening time period and what has not. The group suggest that researchers are making progress in reducing screen fail rates, but not in the critical issues of accessibility and equity.In this excerpt, Jörn asks whether these new, more focused approaches might lead to investigators overfitting patients. The positive of this outcome, he notes, is that sweet spot patients will be in a position to respond to drug. Louise takes on an additional issue: what is the affect of patient lifestyle mitigation on these trials. Her concern: patients who work hard enough to improve their liver condition after learning they have the disease may be so successful that they no longer qualify by the time they would be called for biopsy. The conversation strays into discussing the high value of bring artificial intelligence assists into histopathological interpretation before Stephen returns to the question of recruiting more patients. He notes that the goal is not merely to pull more patients into the first stages o recruitment ("the top of the funnel") but to improve our distribution of different kinds of minorities and subpopulations with high rates of NASH. He points out the fallacy of treating only mainstream Caucasian Americans and assuming results of these trials will hold true for everyone given what we now know about the important of genotyping and mutations tied to race or ethnicity. As this conversation ends, Stephen outlines potential solutions based on shifting recruitment out of brick-and-mortar trial sites and to recruiting and testing at primary care offices or even patients' homes.
THE NASH Tsunami audience came to know Jörn Schattenberg in the Fall of 2020 when he shared a paper he had recently co-authored on why NASH drug trials failed. This week, the same group that discussed that paper – Jörn, Stephen Harrison, Louise Campbell and Roger Green – reflect on what has improved in the intervening time period and what has not. After Roger Green sets the stage for this conversation, Jörn reflects back on the 2020 paper he co-authored with Joost Drenth and considers important changes in patient screening since then. In his own words, “The way we use biomarkers and AI to augment outcomes has changed the field dramatically.” Whereas biopsy used to be the core method used to recruit patients, Jörn notes that many practitioners now rely on NITs to assess the patient's likelihood of screening into a trial before conducting a biopsy. The result is a significant reduction in non-essential biopsies. Stephen follows Jörn by discussing ways his own practice has benefitted greatly from the developing a prescreen strategy that relies heavily on NITs. Instead of doing "five biopsies a day, maybe 25 or 30 a week," he now starts with FAST scores and cT1 and, if these seem promising, moves to multiparametric MRI before deciding who to biopsy. Specifically, his practice is now able to utilize VCTE (FibroScan) and other NITs to mine data in real time and refer patients to the proper clinical trial as a result. As the episode winds down, Stephen alludes to the idea of "mid-trial corrections" in pre-biopsy NIT screening criteria and advances in how biopsies are read in trials today as other areas where procedure has improved markedly.
THE NASH Tsunami audience came to know Jörn Schattenberg in the Fall of 2020 when he shared a paper he had recently co-authored on why NASH drug trials failed. This week, the same group that discussed that paper – Jörn, Stephen Harrison, Louise Campbell and Roger Green – reflect on what has improved in the intervening time period and what has not. The group suggest that while non-invasive techniques (NITs) have made a significant contribution to patient enrolment, there remains reliant on additional screening methods.This conversation opens with Jörn's observation that NITs are not always part of the protocol when assessing patients for their inclusion or exclusion in clinical trials. However, he states, experienced researchers will rely on these tools along with presence or absence of other metabolic diseases to decide which patients should not progress to biopsy due to high likelihood of screening out of the study anyway. Stephen concurs, adding that by considering these other risk factors, the clinical trials benefit from a more enriched patient population. and fewer unnecessary biopsies. From here, Stephen goes on to discuss two other pivotal issues: advance in strategies for reading biopsies and the impact of high screen fail rates on staff morale. On the first point, he states that good drugs have been lost in development because the strategy for reading biopsies, which relied on a single pathologist to read, created interpretative barriers that led to trials failing or being discontinued. This has led to a place today where all trial design incorporate consensus histopathology reads. On the second, he contrast staff performance for two studies on the same drug: an obesity study with a 25% screen fail rate and a NASH study with an 80% rate. He describes the palpable difference how staff feels about working on each of these projects. As the conversation ends, Louise comments on changing FibroScan thresholds for admission to some trials and Stephen describes how inclusion thresholds might vary from trial to trial and ways he uses other NITs to complete his assessments.
THE NASH Tsunami audience came to know Jörn Schattenberg in the Fall of 2020 when he shared a paper he had recently co-authored on why NASH drug trials failed. This week, the same group that discussed that paper – Jörn, Stephen Harrison, Louise Campbell and Roger Green – reflect on what has improved in the intervening time period and what has not. Large metropolises are identified as missed opportunities. Stephen starts this conversation by shifting focus from issues surrounding trial criteria to the challenge of finding the right patients for these trials. He notes that of the millions of patients with NASH in the U.S. today, only a small fraction might ever realistically find their way to a NASH trial. The biggest factor is that they can only find their way to a trial if they live with clear access to a trial center. This is not simply a question of rural and exurban residents having too far to travel. He cites Chicago as a city that contributes minimal patient enrollment, despite being a large cites whose population suffers from high levels of metabolic disease. Jörn adds that while we might believe that European countries with more socialized, government-centered systems would not exhibit this maldistribution in where trial patients live, that belief would be wrong. Roger suggests that the U.S. system, with its highest levels of investment in medical technologies and broader distribution of care sites, might actually be better equipped to attack this issue. At that point, Roger returns to an earlier comment to ask Stephen addresses how mid-trial reassessment of screening criteria works and why it improves screen fail rates. Stephen's answer takes up the rest of this conversation.
THE NASH Tsunami audience came to know Jörn Schattenberg in the Fall of 2020 when he shared a paper he had recently co-authored on why NASH drug trials failed. This week, the same group that discussed that paper – Jörn, Stephen Harrison, Louise Campbell and Roger Green – reflect on what has improved in the intervening time period and what has not. The group suggest that researchers are making progress in reducing screen fail rates, but not in the critical issues of accessibility and equity. As the conversation begins, Jörn harkens back to the 2020 paper and reflects on improvements in cost-effectiveness and duration of the trial process since. “The way we use biomarkers and AI to augment outcomes has changed the field dramatically.” Yet clinical trials are still reliant on the same endpoint. A surrogate is required for conditional drug approval. Roger asks for the most important improvements that have resulted from conversations around patient selection for a trial. Jörn recalls the past reliance on biopsies and compares today's focus on non-invasive techniques (NITs). Stephen joins to highlight improvements in the way practices utilize VCTE (FibroScan) and other NITs to mine data in real time and refer patients to the proper clinical trial. One idea Stephen mentions: evaluating NIT values during the recruiting process to reset cutoff levels. He also discusses expanding screening criteria to include non-hepatic metabolic risk factors such as obesity and diabetes. Both approaches to patient refinement are contributing to more successful studies and limiting unnecessary biopsies. With fewer screen failures, sites remain engaged. Louise Campbell agrees that mitigating screen fail rate is key to fighting study fatigue. The conversation shifts to finding patients for these trials. Stephen notes that major metropolises still do not have access to NASH clinical trials. "We're putting almost zero NASH patients in clinical trials out of a city as large as Chicago that has high rates of obesity, diabetes and metabolic syndrome.” NITs like the FibroScan are unavailable in large swaths of the country. Even where they are available, a lack of education around NASH diagnostics tests remains a barrier. Jörn adds that multiple hurdles prevent patients from accessing NASH trials in socialized healthcare systems. Roger believes the US system may have a better shot than Europe at broadening recruitment processes because the technology developed under larger U.S. budgets means that some pivotal technologies are more widely available.Next, Roger comments that for as long as screen fail rate has been discussed on this podcast, we had never discussed the idea of mid-trial adjustments. Stephen gives an example of adjusting FibroScan thresholds mid-trial to boost the number of eligible patients. Jörn shares his belief that the use of NITs outside the formal qualification criteria has helped reduce screen fail rates.Stephen shifts focus to a bigger issue: equity in the representation of underserved patients in these trials. There is an issue of decentralized trials, whereby at-risk groups are under-referred due to several factors. Stephen outlines potential solutions. Roger suggests tertiary care research universities that have their own primary practice as suitable to become an accessible point of referral. He notes this may not translate to the European system and Louise agrees. What is there to look forward to in this space in 6 months to a year? Louise is looking for the approval of FibroScan for primary care in the UK. Jörn is hoping for an opportunity to offer health care services through referral systems. Stephen says we'll hopefully be a step closer to getting a drug approved. Roger finishes with a Stephen quote: is the juice worth the squeeze? This "juice" takes forms of cash and optimism, and it will be worth the squeeze if a drug sees successful development.
As the NASH pandemic grows in the number and diversity of patient cases, one patient group receiving increased notice includes patients with "lean NASH," those with "normal" BMI levels (BMI
As the NASH pandemic grows in the number and diversity of patient cases, one patient group receiving increased notice includes patients with "lean NASH," those with "normal" BMI levels (BMI
As the NASH pandemic grows in the number and diversity of patient cases, one patient group receiving increased notice includes patients with "lean NASH," those whose BMI levels are "normal." Last month, Gastroenterology published Best Practice recommendations for diagnosing and treating lean NASH. Two of the authors, Drs. Michelle Long and Mazen Noureddin, were good enough to come on the podcast to share the thinking behind this article along with its key observations and recommendations.This conversation starts with Roger Green asking Michelle and Mazen how they came to write this piece and how the paper came together working with co-author, Dr. Joseph Lim. First, as Michelle notes, "we had to all get on the same page," on the issue of the highest BMI that would be considered lean or, more precisely, not overweight. From there, the team outlined 15 Best Practices based on clinical experience, and set out to refine these based on relevant literature and recommendations from colleagues and reviewers. The co-authors note that while little of what they learned while preparing this paper was surprising, it forced them to focus on creating a fairly simple set of stepwise goals for clinicians to follow. Louise Campbell joins the conversation to praise the simplicity and clarity of the Best Practices chart the co-authors created. After noting that this algorithm is not very different from others, Mazen goes on to mention "a couple of things...that we're proud of:" identification of high-risk patients based on age (over 40) or presence of Type 2 diabetes. He also notes that they provided greater clarity around more advanced non-invasive tests like ELF, MAST, FAST, MEFIB, MRI, and cT1.The conversation shifts to focus on the recommendation to retest every 6 or 12 months. Louise notes this approvingly. The group agrees that screening T2D patients annually using FIB-4 is not very different than screening annually for eye, kidney or neurological complications. Roger Green joins the conversation to suggest a 3-5 year follow-up recommendation is not patient-centric, but might calm payers concerned about skyrocketing costs of treating Fatty Liver disease. Mazen shares his expectation that yearly evaluation will be cost-effective and patient-centric. Roger shares an informal belief he has developed that whether due to later stage diagnoses or different disease pathogenesis, lean NASH patients might be more costly because patients progress to cirrhosis more quickly after the original diagnosis. Michelle tends to agree but notes that more research is needed on this.Next, the conversation shifts toward diagnostic approaches. Roger mentions the possible benefit of the "Fibrosis First" method that Ian Rowe discussed the previous week (S3, E39), particularly appropriate when primary care providers observe danger signs in lean patients. Mazen points to extremely elevated liver enzyme levels (ALT of 80 or 90). Michelle agrees, but notes that most of her lean NASH patients are diagnosed in an ED with complications of cirrhosis. The group then spends time asking what might make primary care providers comfortable testing for fibrosis, even if only to pass the patient on to the appropriate specialist. Roger asks what different groups can learn from this paper. Michelle states that this is a clear call for more research. Mazen points to Table 2 in the paper, which lists other diseases that hepatologists should consider when evaluating these patients. He continues to state that the document is helpful for non-hepatologists and hepatologists alike. Finally, he points out that clinical trials are pivotal for these patients. The last several moments focus on how to ask patients about alcohol consumption and then the closing question. Michelle notes the importance of using lists and tables in the paper to guide the special issues in treating these patients.
This week's "Conversation from the Vault" comes from September 2021, when Anthony Villiotti of NASH kNOWledge joined Louise Campbell and Roger Green to discuss what he considered the "biggest Fatty Liver story of the summer."In his answer, Tony pointed to two studies published during the summer. The San Antonio Military Medical Center study confirmed work done a decade earlier that suggested overall NAFLD and NASH incidence in a population of asymptomatic middle-aged Texans (37% NAFLD and 14% NASH) might be far higher than the most common publicly quoted numbers (25% and 5,6%, respectively). As we wrote in our conversation synopsis at the time, "Tony and Louise Campbell agree on the importance of educating children starting in their early years of schooling. Tony also comments on his belief in grass-roots education and hopes that as the COVID-19 pandemic abates, he will have more opportunities to do so. Louise talks about the need to educate/motiave primary care practitioners and related specialists to test more frequently and learn about the role the liver plays in non-communicable metabolic diseases they treat more frequently."
One of the most important challenges facing Fatty Liver stakeholders involves improving early diagnosis for patients with clinically relevant or advanced fibrosis (F2/3). Today, a significant percentage of patients learn they are living with cirrhosis in the Emergency Department during a decompensating event. Four in ten of these patients in the UK do not leave the hospital. Episode 39 reviewed a model that Ian Rowe and Richard Parker developed to determine the most cost-effective strategy for F2/3 diagnosis.As this conversation starts, Louise Campbell notes that John Dillon reported in Barcelona that slightly over half of patients identified as having Fatt Liver via iLFT never returned for their appointments. Ian Rowe points out that this will reduce the costs in the model due to missed diagnoses but questions whether this cost reduction is truly beneficial since missed patient visits translate into non-treatment. More important, he reminds us that iLFT is under constant improvement so that data collected earlier in its lifecycle might not accurately reflect its costs and benefits today.Upon Roger Green's invitation for other questions Louise Campbell asks whether "we" (presumably the UK NHS) should do a better job supporting positive diet and exercise activity for healthcare professionals inside the system. On a more serious note, this leads Ian and Louise to focus on the policy issues that can support patients better (particularly those in the workforce). Ian points out that alcohol is issue #1 for many of these patients. He and Louise go on to point out the importance of public policy around things like soda and sweet food advertising in shifting consumers' focus or craving for bad foods. Roger suggests that this is a two-element issue: stopping advertising for soda and sweets will reduce disease over time but we also need to treat patients who already have developed disease. As he puts it, policy can "put your foot on the hose," but even if we stop the in-flow of new Fatty Liver and metabolic patients, we still have "the patients in the hose" and they will need therapy. As a final thought before wrap-up, Ian shares his belief (which Louise also holds) that VCTE might be more effective in causing changes in patient behavior than blood tests, even if they point up the exact same patient need. The difference: feedback from VCTE comes in real-time where patients get face-to-face feedback and respond, whereas bloodwork results comeback to the patient several days later and delivered impersonally. From here, the group moves to the wrap-up question, which addresses research we should be doing and action steps/changes in behavior we should be promoting. You will have to listen for yourself to hear Surfers' answers.
One of the most important challenges facing Fatty Liver stakeholders involves improving early diagnosis for patients with clinically relevant or advanced fibrosis (F2/3). Today, a significant percentage of patients learn they are living with cirrhosis in the Emergency Department during a decompensating event. Four in ten of these patients in the UK do not leave the hospital. Episode 39 reviewed a model that Ian Rowe and Richard Parker developed to determine the most cost-effective strategy for F2/3 diagnosis.This conversation centers around challenges related to early diagnosis and NASH Patient Management. As Roger Green notes, listeners to NASH Tsunami might recall a significant number of conversations in which patients and advocates complain about doctors telling them "not to worry" about their Fatty Livers for years until the condition progresses to cirrhosis. Louise Campbell focuses on a different challenge: that of NASH patient management when patients are dealing with other metabolic diseases that are better known or where approved treatments exist.
One of the most important challenges facing Fatty Liver stakeholders involves improving early diagnosis for patients with clinically relevant or advanced fibrosis (F2/3). Today, a significant percentage of patients learn they are living with cirrhosis in the Emergency Department during a decompensating event. Four in ten of these patients in the UK do not leave the hospital. Episode 39 reviewed a model that Ian Rowe and Richard Parker developed to determine the most cost-effective strategy for F2/3 diagnosis.This conversation starts with Louise Campbell agreeing with the vision that led Ian and Richard to build this model. She notes recent data she heard that 85% of all US patients with cirrhosis (and 55% in the UK) learn their diagnoses for the first time in an Emergency Department, which suggests the need to improve earlier diagnosis. She notes that some UK programs are widely cited as examples of good (or best) practice, but, more important, notes that these have been cited as examples for a long time, but also notes that other regions and hospitals have not emulated them. She goes on to ask how the efficiency and number of patients captured in the model would increase if the target expanded to include all patients with metabolic disease. Ian notes that these patients were not included in the model and also suggests that the question reflects a larger question about the goal of this kind of screening.
One serious challenge in the overall management of Fatty Liver disease involves creating cost-effective methods for "early" diagnosis. The term "early" is relative because, as Ian Rowe puts it, a "substantial proportion" of people admitted to hospital with various symptoms of decompensating cirrhosis or hepatic encephalopathy never received a diagnosis of advanced liver disease before they presented. Simply diagnosing these patients during advanced fibrosis (F2 or F3) can save lives, improve longevity and quality of life for these patients and save money for healthcare systems, all at the same time. Ian spends the first ten minutes of this episode describing a model he and Richard Parker developed to evaluate five diagnostic strategies:Targeted -- simple non-invasive liver screening Targeted + risk stratification -- targeted assessment plus FIB-4 or VCTE (FibroScan) for patients believed to be at high riskiLFT -- automated assessment of abnormal LFTs analyzed with other systemic measures in a medical record system "Comprehensive" -- a "kitchen sink" approach that runs iLFT analysis and conducts FIB-4 +/- VCTE on every patient"Fibrosis first" -- an approach that deploys viroserological and iron testing plus FIB-4 +/- VCTE for every patient "Fibrosis first" scored best in cost effectiveness (cost per correct diagnosis of treatable liver disease) and "decision curve analysis", which looks at true positive outcomes and false positive outcomes, correctly identifying 85% of treatable liver disease patients (vs. 90% for the comprehensive approach and less than 15% for the current targeted approach.) Fibrosis first has the added benefit of not progressing treatment for people who may have steatosis without fibrosis. The rest of the conversation entails Ian, Louise Campbell and Roger Green sharing questions and observations. Highlights:Louise agrees that the current targeted pathway approaches do not work and identifies lack of access to advanced testing in primary care as a central issue. She asks how many additional patients with Type 2 Diabetes, other metabolic diseases or CVD could be identified through this approach. Ian cannot answer because the question is outside the scope of the research. He points out that to assess different approaches accurately, researchers and policymakers need to settle on whether the goal is to identify steatohepatitis or something broader. Louise asks about the frequency and nature of referrals. Ian notes that one issue with iLFT is a high level of referrals for conditions that might not require treatment, the most common of which is "abnormal LFT without fibrosis."Roger notes that iLFT might help patients who complain they never heard about their NASH earlier. He also recalls Quentin Anstee and Stephen Harrison discussing recently that FIB-4 can serve as a prognostic measure not only for liver-related deaths, but also CV deaths and all-cause mortality. Louise suggests that patients will do better if they adopt a behavior belief model instead of a sick patient approach and that the earlier in disease we intervene, the more success we will have. Roger and Ian note that Louise's focus is broader in scope than his model. Ian further notes that we do not know when non-fibrotic patients should be tested again, although he has some thoughts about this. Louise notes that one element that might make iLFT costly is that only 45% of patients picked up on iLFT are referred into the model. Ian notes that this insight might require changes in the model.As the conversation winds down, it shifts toward policy issues: should we focus testing on the workforce (Louise) and it the best point of intervention to limit advertising of unhealthy foods (Ian).
Our week of "Greatest Hits" episodes from the vault continues with this conversation from the episode announcing the launch of the NAIL-NIT consortium. Stephen Harrison and Mazen Noureddin discuss the thinking behind their new consortium and its targets. In this conversation, they discuss challenges with the NAS score.The early part of 2022 had several episodes discussing the increasing need to move beyond biopsy (yes, semi-quantitative, but even AI-assisted at some levels) to a future shaped by NITs. One pivotal issue that emerged regarded ballooned hepatocyte evaluation and its impact on NAS scores. As I wrote: The first section focuses mostly on what we can and cannot learn from a NAS score, and implications of its shortcomings on the drug development process. After this, Stephen Harrison notes the complex role the liver plays in energy transfer throughout the entire metabolic process. This suggests that the effects of Fatty Liver disease vary among individual patients and, as a result, drug development and patient diagnosis and treatment should provide sufficient insight to optimize each patient's therapy. As the conversation closes, Mazen Noureddin is responding to a question from Louise Campbell about what we will learn about optimal testing strategy. Mazen suggests there is unlikely to be a single "winning" test but, instead, a combination of NITs probably will be necessary to answer all the questions necessary to optimize therapy.
Our week of "Greatest Hits" episodes from the vault continues with our second most popular conversation ever, which came from the wrap-up episode for AASLD2021. In this episode, Manal Abdelmalek, Jörn Schattenberg and Ian Rowe joined Stephen Harrison, Louise Campbell and Roger Green to recap NAFLD and NASH-related insights from AASLD2021 TLMdX and specifically to focus on how NITs will help, in the words of Stephen Harrison, "put a big, fat dent in Fatty Liver disease."As I wrote at the time: The conversation starts with the group congratulating Manal Abdelmalek on her wrap-up NAFLD talk at the 2021 TLMdX. From there, the group focuses on the shortcomings of using biopsy as the clinical trial gold standard and how strategic clinical trial design and interpretation of existing NIT data can build a bridge from biopsy through MRE/biopsy correlations to a total NIT future.
his week, Surfing the NASH Tsunami returns to a subject we have explored from time to time over the past two years: helping patients with cirrhosis. While the immediate stimulus for doing so was the semaglutide late-breaker at #ILC2022, our more general interest is that many patients with cirrhosis will start to decompensate and decline in a fairly short period of time. This conversation brings together key threads from earlier in the episode, focusing significantly on providing better cirrhosis patient support as a key element in improving NASH cirrhosis therapies.As this final conversation starts, Jörn Schattenberg and Lars Johansson are discussing two points: (i) the idea that even when a patient is diagnosed, this might not make it into that patient's medical record or become a focus of therapy, and (ii) the idea that the 30,000-patient study Lars has mentioned is focusing on deriving outcomes without biopsying patients. Louise Campbell joins in to endorse both these ideas, focusing more on capturing patients' NAFLD, NASH or NASH cirrhosis in the medical record and making it actionable. In particular, she notes that the investment necessary to improve communication will be far lower than what will be necessary to create or dramatically enhance drugs and diagnostic technologies.This leads to Roger Green's closing question about a likely area for short-term improvement in a treatment area the panelist touches every day. Panelists' answers are diverse and thought-provoking.
This week, Surfing the NASH Tsunami returns to a subject we have explored from time to time over the past two years: helping patients with cirrhosis. While the immediate stimulus for doing so was the semaglutide late-breaker at #ILC2022, our more general interest is that many patients with cirrhosis will start to decompensate and decline in a fairly short period of time. This conversation focuses on what Roger Green describes as a "pincer movement" in technological development: high-end technology to empower better diagnosis, staging and treatment and low-end technology to capture more patients, capture them earlier in disease and keep them engaged in the process.The conversation starts with Roger posing a question of whether the major need in improving cirrhosis diagnosis and treatment is a human systems or a medical technology issue. After some conversation, the answer turns out to be "both."Louise Campbell responds first. She focuses on human systems needs: send the right letter, engage the patient and provide the proper and necessary information to educate the patient and keep them involved. She goes on to note that (i) these needs appear to be global in scope although the challenge takes different forms in different countries; and (ii) for patients with progressive disease, "not feeling worse" is an outcome they will pursue aggressively. This observation, coming after earlier discussions about medical treatment issues, leads Roger to make his "pincer movement" comment. Jörn Schattenberg agrees that there is a "disparity" between investment in high-end medical technologies and physician and hospital office systems that rely on older technology and inadequate systems. He states that he considers it important to invest in health structure improvements as well as advancing technologies.Roger asks Lars what role high-end technologies will play in advancing patient care. Lars suggests that technology's major role will be in driving better decisions about which drugs to develop and how. He goes on to state that advances in clinical practice need to be simple, affordable and practical. The example Lars gives is an effort years ago to persuade Swedish patients with dyslipidemia and cardiovascular disease to focus on Apo B instead of LDL. The task became impossible because, in spite of more compelling data on Apo B, the concept of LDL-lowering as the therapeutic target was so well embedded that it proved impossible to dispel, or even modify meaningfully. As this conversation winds down, Roger asks Lars to describe work he is doing that will benefit patients. Lars talks about exploring the effects of cirrhosis on other organ systems, specifically the heart and kidney. Jörn follows up with a question about deploying standard imaging (his example is back pain) to identify previously undiagnosed liver issues. Lars responds by discussing an AI-aided study he is working on with 30,000 patients looking at multi-organ imaging issues using CT. He suggests that in the future, simply having a section of liver in the CT will provide this kind of guidance.
Surfing the NASH Tsunami has explored issues of NASH cirrhosis since our earliest episodes in 2020. This episode integrates panelists with three different perspectives to consider the most important challenges in treating patients with NASH cirrhosis today. Jörn Schattenberg was an author of the #ILC2022 late-breaker presentation discussing semaglutide in NASH cirrhosis. Antaros Medical co-founder and Chief Scientific Officer Lars Johansson has discussed and published on different ways to evaluate the impact of medications on cirrhosis. Louise Campbell's career in nursing and subsequent work at Tawazun Health has focused on providing patients with the information and support they need to improve their own conditions.Roger Green starts the dialog by recounting the cirrhosis discussions over the life of the podcast, starting with discussions about using older medicines (statins, metformin) that might benefit patients, a significant number of which might decline relatively quickly. Jörn Schattenberg picks up this line of discussion, then goes on the describe the semaglutide late-breaker at ILC2022. Jörn notes that while the study failed to achieve fibrosis regression in 48 weeks, it improved a range of metabolic markers while demonstrating a strong safety profile in this population. Jörn goes on to note the importance of early (okay, earlier) diagnosis in these patients and notes that ELF is indicated in the US and EU to confirm a diagnosis of cirrhosis. Lars Johansson joins the conversation to ask Jörn whether he believes 48 weeks is enough time to expect fibrotic regression in cirrhotic patients. After Jörn concurs, Lars comments that effects seen with sema in this population (20-30% reduction in spleen volume and early signs of portal pressure changes) suggest we are "doing something good" even if the drug did not regress fibrosis within the study period. Lars goes on to discuss triggers that tell him how well (or poorly) the liver and overall metabolic system are working in a target patient. When evaluating other diseases (heart, kidney), he points out, we look directly at organ function. With liver, he notes, we look at biopsies.At this point, Roger asks the group where the next breakthrough in cirrhosis therapy is likely to occur. Louise points to the need to improve patient communications, given how many patients do not learn they have ANY liver disease until their initial cirrhosis diagnoses. Jorn states that a key to improving communications and educating front-line physicians is to create simple, automated measures that will allow the patient's risk status to appear on an electronic medical record. Lars foresees a major breakthrough when we can study imaging results along with circulating biomarkers in order to identify a single biomarker (or a small group of them) that can predict advanced disease. Louise returns to the point that without improved communications, we will fail to keep patients engaged in their own therapy, which will have severe consequences. This leads Roger to describe the next stage as a "pincer movement," with high-tech diagnostics and new drugs on one end and better human systems engineering and electronic communication on the other. Next, Roger asks Lars where he believes what he is learning will translate into improved diagnostics. Lars and Jörn agree that the best strategy is a first stage of inexpensive screening to rule out patients without disease, and then probably a CT-based evaluation to appreciate the status of the liver and impact on related organ systems. As the conversation wraps up, Roger asks where each panelist sees the greatest potential for growth in the next 1-2 year. Louise and Jörn focus on improved patient communication and simple screening, while Lars talks with excitement about starting to garner large amounts of data from some of the large, long-term outcome studi
On July 7, Intercept Pharmaceuticals released new results from the continuation of the REGENERATE trial and announced their intent to file a new NDA for obeticholic acid (OCA) in NASH fibrosis. In this conversation, Stephen Harrison leads Jörn Schattenberg, Louise Campbell and Roger Green in considering whether the evidence in the new release will be sufficient to get the drug approved.Stephen starts by noting that we have not heard anything about the results of the REVERSE trial, which evaluated obeticholic acid (OCA) in patients with compensated cirrhosis. As he notes, even if OCA is not approved for cirrhosis, many hepatologists will consider giving this drug to cirrhotic patients, particularly compensated cirrhotics who face a significant worsening of their condition in a fairly short period of time. Jörn comments on this briefly to agree that the cirrhosis data will create a complete data set, then returns to the pruritus issue. Mostly, his point about cirrhosis is that given the high placebo rate suggests there is "something about how the question is asked." He finishes this comment by discussing the importance of getting a first drug approved and stating his anticipation of what happens when FDA reviews these data. Roger goes on to note that he has a unique experience in this group: he has discontinued a drug therapy based on pruritus (in his case, a cancer drug). Having lived through that experience, he expresses skepticism that pruritus that resolves on discontinuation will be a reason for the drug to be rejected. Stephen concurs, and Roger goes on to state that the perceived cardiovascular risk in 2020 made sense as a reason not to approve, but not pruritus. Stephen and Louise concur that we will not know the entire story until we know the lengths to which providers went to keep patients in this study, but both are hopeful (and pretty much expect) that while there may be boundaries on patient types and guidance on treatment, the case for approval appears likely to succeed. During the second half of this conversation, panelists share their common hope that this data will be sufficient to get OCA approved and discuss what this could mean for the entire Fatty Liver stakeholder community.
On July 7, Intercept Pharmaceuticals released new results from the continuation of the REGENERATE trial and announced their intent to file a new NDA for obeticholic acid (OCA) in NASH fibrosis. In this conversation, Stephen Harrison leads Jörn Schattenberg, Louise Campbell and Roger Green in considering less obvious questions surrounding efficacy and safety.Stephen starts this conversation by asking the group how important it is for a drug (in this case, obeticholic acid) to show a combined endpoint of fibrosis improvement and NASH resolution. He notes this is a tougher standard to hit but notes that it might be quite important.Jörn describes this comment as a "good point" that probably was not addressed due to the low level of NASH resolution when viewed as a primary endpoint. Louise says she would need to know more about the diets patients were on while in the trial given the effect diet can have on liver fat. She then goes on to say that one question she would like to have answered is how many patients needed counseling on their pruritus to stay in the study and what exact steps did researchers take to keep these patients in. She points out that knowing the steps necessary to maintain patient adherence is vitally important to caregivers but rarely reported for trials, if ever.Roger makes two points. His first basically supports Jörn's comment that the low level of NASH resolution as a primary endpoint virtually guarantees that the number of patients achieving the dual endpoint will be minimal at best. His second harkens back to Stephen's earlier point about including a larger post-18 month patient pool in the efficacy analysis. To Roger, it appears that Intercept made the sound commercial decision to reveal only the data necessary to generate the analyses necessary for approval. It felt to him as if Intercept assessed the least risky way to refute each point in the CRL, and then did only the analyses necessary to refute points successfully. In essence, Roger describes the analysis as a way to de-risk the drug and believes they appear to have done so effectively. At this point, Stephen shifts direction. He gives Intercept "accolades...they didn't give up. They persevered. They continued to drive forward and they added three different adjudication committees." And while he believes there is more analysis to be done, he describes the contents of the press release as "a very, very positive implication for the field" and "give[s] it two thumbs up." After Roger concurs, Stephen goes back to Louise's questions about pruritus and notes that the methodology for evaluating pruritus might have produced overstated results. In essence, the investigator asked patients whether they were experiencing pruritus at every visit, an approach Stephen and Jörn believe was likely to produce an overstatement on itching. Stephen continues this line of thinking to note that investigators were forced to discontinue therapy under certain pruritus reports. As the conversation ends, he notes that he is far more interested in hepatic effects.
On July 7, Intercept Pharmaceuticals released new results from the continuation of the REGENERATE trial and announced their intent to file a new NDA for obeticholic acid (OCA) in NASH fibrosis. In this conversation, Stephen Harrison leads Jörn Schattenberg, Louise Campbell and Roger Green in examining the new efficacy analysis and exploring what it means for obeticholic acid, both in terms of the drug's performance and its revised prospects for FDA approval.After reviewing the four key points from Intercept's press release, Stephen Harrison kicks off this conversation by looking at a broader efficacy picture than mere regression of fibrosis, to ask what percentage of patients experienced no further progression of fibrosis compared to the placebo group. Stephen notes that the clinical value of simply halting fibrosis progression in an F3 patient is tremendously important because it allows an asymptomatic patient to continue life at its current level of quality. He adds, "we can manage co-morbidities" separately. He goes on to wonder why Intercept did not expand the analysis to include the large number of patients who made it past the 18-month biopsy time point but were not part of the original 2019 efficacy cohort.At this point, Stephen takes a step back from the actual data to describe how the consensus approach worked on histological reads and to praise the approach for providing clear, simple answers. Jörn Schattenberg picks up the conversation by agreeing with Stephen's assessment of the consensus approach, which he describes as emulating how colleagues assess challenging cases or histopathology reports in actual practice. Roger joins the conversation to wonder why the consensus reading process would have the effect of reducing the percentage of patients who improve in the placebo group on one reading but not elsewhere. More important to him, he goes on to agree with the idea that if this agent regresses fibrosis in some cases but halts progression in most or all, it might become a valuable part of a combination therapy that includes other agents with a stronger effect against steatosis than fibrosis. Thinking from a patient perspective, Louise notes that consensus reads should give the patient greater confidence in the results. In terms of confidence and border reads, Stephen points out that some of the presentations at the recent ILC2022 meeting that drugs that have an impact on NASH might also affect liver volume. (He notes that the open-label cirrhotic cohort of the resmetirom trial MAESTRO-NAFLD 1 also showed spleen volume reduction and an inverse effect on platelet count.) Setting aside the cirrhosis results, he notes that if we start to measure liver volume when conducting biopsies, we can correct estimates of the impact of fibrosis to account for changes in "what we see" based on changes in liver volume. As the conversation ends, he notes that this might be a fruitful topic for future research that can translate into patient treatment.
On July 7, Intercept Pharmaceuticals released new results from the continuation of the REGENERATE trial and announced their intent to file a new NDA for obeticholic acid (OCA) in NASH fibrosis. In this conversation, Stephen Harrison leads Jörn Schattenberg, Louise Campbell and Roger Green in examining the new efficacy analysis and exploring what it means for obeticholic acid, both in terms of the drug's performance and its revised prospects for FDA approval.After Stephen lists the four major bullet points from Intercept's press release, this conversation focuses on the first point: "The 25mg dose of obeticholic acid met the agreed primary endpoint of improvement in liver fibrosis without worsening of NASH at 18 months." The data behind this bullet point stem from a new interim analysis of the original 931 cases. In the re-analysis, the treatment effect remained constant but the placebo effect dropped slightly. The different results from a different method of analyzing histopathology, one that relied on consensus panel reads instead of an individual histopathologist's interpretation (as was done in the original analysis). Stephen goes on to note that there is a similar small change in the NASH resolution percentages, but, like the original analysis, these do not reach statistical significance. He notes that this submission relied on hitting one of the primary endpoints, not both of them. He then asks the group two questions: "Does this change our perception of OCA in NASH?" and "Does this change our perception of this drug as a driver of the field in drug development for NASH?"Roger answers first. Taking a narrow focus on the question, he answers that we still see OCA as an effective anti-fibrotic at the same level we did three years ago. If there is a change, it is that if obeticholic acid had a three-year lead on the market, it would have focused a significant amount of research on FXR agonists -- both in terms of developing more FXRs and in considering them the backbone in NASH pharmacotherapy. In 2022, with another very different agent appearing to be fairly close to market, he felt these results would not dramatically change the other directions in which research is heading.Jörn Schattenberg goes back to the original 2019 paper, which he describes as "groundbreaking" and, quoting Zobair Younossi, "a watershed moment." He notes that the reading method seems more consistent with what FDA wants and says that while others may comment on the small effect size (11%), his view is that this is a positive achievement as the first paper to demonstrate significant effect against fibrosis.Louise Campbell echoes her colleagues' comments about the successful efficacy results but notes that patients who could have benefitted from OCA's approval two years ago have gone two more years without the benefit of medication.Stephen concludes the conversation by agreeing with Jörn that this is a watershed moment. He notes how many observers have said that proving efficacy was essentially impossible due to the complexity of the disease and regulators "moving the goalposts." This study, he says, proves that it can be done.
On July 7, Intercept Pharmaceuticals released new results from the continuation of the REGENERATE trial and announced their intent to file a new NDA for obeticholic acid (OCA) in NASH fibrosis. In this conversation, Stephen Harrison leads Jörn Schattenberg, Louise Campbell and Roger Green in examining how the larger sample and longer time patients were on therapy changed the safety and tolerability profile from the initial analysis.After reviewing the four key points from Intercept's press release, Stephen Harrison kicks off this conversation by discussing the safety evaluation, which included a far larger population with significantly longer exposure to study drug. After describing the enriched population, he quotes from the press release, "Emergent adverse events treatment, emergent serious adverse events, and deaths were generally balanced across the OTC and placebo treatment groups." He goes on to cite the considerable differences in pruritus across groups (22% in placebo, 33% in 10mg and 55% in 25mg), share the comment that most discontinuation stemmed from pruritus, note that gall bladder-related events occurred in less than 3% of patients and, finally, that OCA 25mg had a higher rate of biliary events. He then asked the rest of the group for comments.Jörn commented first, noting that this was mostly "recapitulated" data, but with a much broader set of subjects. Because risk:benefit ratio was perceived as the pivotal issue around the time of the original Complete Response Letter (CRL), he describes the data as improved "by a lot."Louise describes as "reassuring" the idea that the NASH dose could be so much higher than the approved PBC dose (25mg vs. 5 or 10mg) but not demonstrate additional safety concerns. She goes on to declare that practices planning to use OCA should be "planning pathways into delivery" in anticipation that the high level of pruritus will lead to a significant set of discontinuation with a careful approach to patient orientation and management. Roger shared his recollection that increases in LDL levels and the implicit associated cardiovascular risk were major issues in the negative risk:benefit assessment, but that this analysis appears to report that levels returned to normal within the first year of treatment. This might increase chances for approval.At this point, Stephen reads the press release carefully to identify potential safety hazards that are not addressed directly in the document, although, as he notes, one can fit only so much into a press release. As the conversation ends, Stephen asks Jörn if he has "ongoing lingering questions". Jörn notes that he wondered how the reads were done and that he also looked for LDL data. He makes a few other points, but suspects that they may have been covered in the 2019 paper.
Last month, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022.) On Thursday afternoon, Scott Friedman chaired an abstract session discussing advances in the basic liver science of researching and understanding mechanisms surrounding fibrosis and stellate cells. Later, he described it as "one of the most exciting groups of presentations I've seen in many years." After this extremely rich and engaging discussion of advances in research processes and the findings the group discussed, Roger Green asked the group with the impact of advances like these will be over the next "year, three years, five years."The answers vary significantly from one panelist to another, in each case reflecting where the panel members touch the healthcare system and product industries. Scott discusses the ability of research to create completely new classes of therapies with previously unimaginable impact on disease, citing CAR-T as one example that is already in use. Louise Campbell makes a vastly different but very important point: it will work better for everyone if we can create more tissue samples, and the ability to generate these kinds of advances will make it easier for providers to ask patients to provide tissue samples and will increase the number of patients who say, "Yes." Scott and Neil both note how good and important a point this is, with Neil stating that the growth in data we can produce from tissue is "exponential," and that this data is key to creating better disease understanding, diagnostics and drugs. Rachel discusses two key areas where the cost of research is decreasing: the availability of open-source data sets and the cost of actual sequencing. Jörn suggests that having a richer understanding of disease will reduce the number of drug failures, partly because we will know how to capitalize on what we are learning and partly because we may not rush into major drug trials where we lack elements of basic understanding. Roger closes with two summary points: (i) that the technologies the group discussed will be applicable not only for NASH but an array of other liver diseases, and (ii) that over the past three years, the field has created a vastly larger number of data points which is starting to look less like scattered points and more like connected dots making an actual picture.With these final notes of optimism and energy, the group closed the discussion.
Last month, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022.) On Thursday afternoon, Scott Friedman chaired an abstract session discussing advances in the basic science of researching and understanding mechanisms surrounding fibrosis and stellate cells. Later, he described it as "one of the most exciting groups of presentations I've seen in many years." This presentation centers on the relationship between Circadian rhythms and stellate cells.It is widely known that we all function under a set of Circadian rhythms tied to day/night changes. Original work in this area focused on physiological changes linked to the central nervous system. In recent years, researchers have learned that other tissues in the body operate on their own Circadian rhythms, presumably tied in some way to the central nervous system. But as Scott exclaims when beginning this discussion, "who would have thought that that included the lowly little hepatic stellate cell, a fibrogenic cell that contains the same mechanisms and the same machinery to regulate circadian rhythm as all those more specialized neuronal tissues." Scott goes on to provide greater detail on the mechanisms through which stellate calls control fibrogenic activity in a cyclical manner. When he concludes, the rest of the group shares comments. Neil Henderson notes that Circadian rhythms are strongly tied to fibrogenic processes throughout the body. Jörn Schattenberg, Louise Campbell and Rachel Zayas comment in different ways on the relevance of circadian rhythms to elements of patient care today, and Roger Green asks a question that leads Scott to note that TGF beta, which he described as "the mother of all fibrogenic cytokines," was the signaling mechanisms for this process.
Last month, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). This episode focuses on an abstract session Scott Friedman chaired on Thursday afternoon discussing advancing in the basic science of researching and understanding mechanisms surrounding fibrosis.Scott starts by describing the session he co-chaired with Sophie Lotersztajn of INSERM as "one of the most exciting groups of presentations I've seen in many years." During this episode, he leads the rest of the panel through exploration of all six presentations. These include:--Targeting the liver circadian clock by REV-ERB-alpha activation improves liver fibrosis by circadian gating of TGF-beta signaling, Atish Mukherji, University of Strasbourg. Scott describes this presentation, which demonstrates that stellate cells have a circadian clock, as "one of the most surprising results" in that circadian activity can be linked to the "lowly stellate cell." This paper generated significant conversation among the group, ranging from Neil Henderson's observation that circadian regulation is a powerful regulator of fibrotic processes to Jörn Schattenberg's observations about what this might mean for treating patients in the clinic to Roger Green asking whether this concept might be germane to specific drugs in development (Scott had mentioned that signalling occurred through TGFbeta. Louise Campbell and Rachel Zayas add comments about the relevance of circadian rhythm to care today and ways this paper might yield exciting new areas for research.--Stellate cell dynamics in progression and regression of hepatic fibrosis, Laura Almale del Barrio, Denmark. This presentation, funded in part by Novo Nordisk, focused on how mouse livers respond when researchers stop injuring them. It leads Neil to comment on how little attention researchers pay to scar healing relative to how much more they pay to the process of scar creation and injury. In response to a question from Scott, Neil also discusses how advances in spatial transcriptomic will make questions like these easier to research in the not-too-distant future. After this, Jörn goes on to note that the paper discussed 14 different stellate cell states, which he interprets as involves activation and transitioning processes. He asks what this might imply for treating patients in the clinic.The other four presentations engender a similar level of exploration. They include:--Peroxidasin deficiency re-programs macrophages toward pro-fibrolysis function and promotes collagen resolution in liver, Mozhdeh Sojoodi, Mass General Hospital and Harvard. --Machine learning methods for detailed characterization of TGF-beta-induced signatures in a large iPSC-derived hepatic stellate cell cohort, Kara Marie Liu, Insitro, United States--The proteomic analysis of hepatic stellate cell differentiation from iPSCs identifies RORalpha as an antifibrogenic target, Raquel A. Martinez Garcia de la Torre, Spain--Biliary epithelial cell-specific RAGE controls ductular reaction-mediated fibrosis during cholestasis, Macrina Lam, GermanyIn each case, Scott starts by discussing the historic of scientific progress that predates the particular paper and topic, places the presentation properly within that context, and invites the others to comment. Each Surfer has unique (and uniquely interesting) comments in their own areas of expertise.
Last week, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). The first three days of the program focused on a range of issues, with specific emphasis on non-invasive tests (NITs) and their role at different stages in diagnosis and treatment. This conversation touches on the impact that NAFLD has on patient quality-of-life and the importance of integrating quality-of-life issues and metrics into everything from clinical trials to treatment protocols.This conversation starts with an observation from Jörn Schattenberg about the importance of looking more carefully at quality-of-life metrics, both in terms of patient treatment and clinical trial outcomes. MIchelle Long, making a closing comment, notes how much more collaborative researchers in the meeting are compared to years past. She then makes an announcement about a major, exciting change in her career, and then exits the conversation.Zobair Younossi identifies "fatigue" as the patient-reported outcome from NAFLD that links most closely to quality-of-life issues He points out that fatigued Fatty Liver patients produce lower quality-of-life scores and also exhibit higher levels of mortality. He goes on to note that fatigue is also linked to unemployment and underemployment, which means that it has clear economic costs. Roger Green asks whether payers will accept economic analysis on this and, as a result, pay for therapy. Zobair suggests that this will depend on whether advocates can make this issue part of the policy, which will drive individual payers' behavior in the US and shape government policy elsewhere. In response to a question from Roger, Louise Campbell comments that the policy environment in the UK is not very different from the US despite differences in how care is actually paid for. She goes on to identify one challenge in this issue, which is that quality-of-life scores decline as soon as a patient becomes aware of their disease, which has the potential to complicate employee analyses when the employee is not yet a patient. She also agrees with Zobair's earlier statement that he would prescribe a slightly more expensive medication if it improves quality-of-life. Zobair closes this conversation by returning to discuss the importance of fatigue and describing himself as "heartened" that fatigue is now measured in most (if not all) clinical trials.
Last week, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). The first three days of the program focused on a range of issues, with specific emphasis on non-invasive tests (NITs) and their role at different stages in diagnosis and treatment. This conversation touches on two issues: how proper use and explanation of NITs can increase patient motivation and why adding NITs to quality measures can have such an effect on educating providers and increasing treatment.This conversation starts with Michelle Long and Louise Campbell discussing studies that demonstrated that patients receiving a FibroScan changed behaviors in ways that lasted at least six months, whether or not they learned they had liver fat. From here, Zobair Younossi discusses the importance of front-line, primary care screening with FIB-4 for all patients with diabetes. Zobair suggests that we consider making use of FIB-4 as a test for co-morbidities in diabetes a formal quality measure, in the same way that providers are required to check creatinine to assess possible kidney damage. Michelle and Roger Green added to Zobair's comment to discuss the specific benefits of adding an electronic health record-generated FIB-4 test as a standard assessment for diabetic patients. Zobair goes back to the point that we need primary care to serve as a front line for diabetes testing. In this context, he suggests the importance of FIB-4 and gives reasons he believes FibroScan will never become widely used in primary care. Louise Campbell disagreed, saying that having FibroScan in primary care would educate patients and drive better care. Jörn Schattenberg discusses some sessions where the consensus supported early FIB-4 use. Roger Green wraps up this conversation by talking about the importance of having formal quality measures around FIB-4 use in the US by telling a story from his own medical history.
During last week's #ILC2022 meeting in London, Louise Campbell took the opportunity to sit down with PBC Foundation CEO and Fatty Liver patient Robert Mitchell-Thain to discuss patient engagement from their own perspectives, Louise as a longtime hepatology nurse (and NAFLD nurse) and Robert as a patient advocate and NAFLD patient.In this conversation, Louise and Robert start by discussing items that have "rocked their world" from this meeting. Robert starts by commenting on presentations that suggest how many patients get missed with a FIB-4 or ALT and expresses the hope that we will improve screening processes to find more people quickly. From there, the conversation shifts toward the role of stigma in patient communication. Specifically, Robert notes about "internal" stigma, the discomfort that patients have discussing their own issues of weight and appearance or sexual dysfunction. Specifically, he states that patients need to "lead from the front" by bringing the statements out in the open, which will make it more obvious that physicians and nurses need to raise these issues during initial visits. It will also push these issues into clinical trials, where we can learn about frequency. Robert notes that nurses have unique value: physicians care about metrics and medical numbers, patients care about quality-of-life, and nurses has the knowledge and skills to bridge between the two. In closing, both agree that patients need to be bold and up-front about their issues instead of, as Louise notes, surrending all accountability once a person allows herself to be define as a patient.
During last week's #ILC2022 meeting in London, Louise Campbell took the opportunity to sit down with PBC Foundation CEO and Fatty Liver patient Robert Mitchell-Thain to discuss patient engagement from their own perspectives, Louise as a longtime hepatology nurse and Robert as a patient advocate and NAFLD patient.Robert starts by discussing his own experience with Fatty Liver disease. First, he notes the importance of patients boldly defining themselves as patients and taking ownership of the word "Patient." As he notes, doctors are only involved with patients during brief, infrequent office visits while patients themselves live the part every day when making a range of decisions about their healthy (or not so healthy) lives. Louise describes her excitement at seeing the data the British Liver Trust, Echosens and e-Scopics have collected while testing people at the meeting. She goes on to mention data from the MAESTRO NAFLD-1 trial, where patients skipped an average of two months of doses due to logistics related to the COVID-19 pandemic, but still showed clinical benefit. Sharing that kind of data with patients might make them feel more comfortable resuming medication after one (or a few) missed doses. Robert goes on to discuss his own "day of diagnosis"...his reaction to the suggestion about losing 10-15% of his body weight and his recognition that the patient's urge at a moment like that is to "fight or flight." He goes on to note that this kind of emotional response is not solution-oriented so that patients and providers alike would do well to consider revisiting how to achieve goals like 10% weight loss at a more rational moment when the patient can focus on solutions. (Robert reminds us that from the moment the patient receives a diagnosis until they leave the physician's office, they fail to retain 40-70% of what they have been told.) In the end, Robert would like to see more patient experience and patient involvement presentations next year, while Louise hopes for a successful NASH drug Phase 3 study that might point the way toward approval. They go on to discuss some issues around PBC before wrapping up the conversation.
Last week, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022,) the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris NASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not). On the last full day of the program, several vitally important drug development studies were presented during the late-breaker and dedicated sessions. The conversations in this episode will review some of the most important findings. This particular conversation includes reactions to the two major resmetirom presentations from the rest of our panel.It starts with Jörn Schattenberg responding to the spleen and liver volume statements in Stephen's presentation. He signals partial agreement and acceptance, then goes on to comment on ways the study methodology might have led to clearer volume data to interpret. In the end, though, he notes that other papers have linked spleen volume to clinically significant changes in portal hypertension. Stephen acknowledges Jörn's comments and suggests that the upcoming MAESTRO Outcomes study might be an excellent place to resolve these issues. Mazen Noureddin provides a more upbeat assessment of this data. He notes that when treating patients, the positive signs he seeks are reduction in spleen size and liver volume accompanied by a change in platelets. Since all three of these occurred in the cirrhotic cohort, he is somewhat optimistic about what future studies will prove. On the MAESTRO NAFLD-1 Phase 3, he states that this is the first trial he can recall (perhaps the first, period) where MRE is reduced. He "hopes this is fibrosis" and is excitedly awaiting confirmation when biopsy results are released.Michelle Long agrees with Mazen and further notes that in the non-cirrhotic trial, the idea that patients missed two months of doses made the results more "generalizable" to what we might expect in standard clinical practice. Louise Campbell follows this up with the statement that many MAESTRO NAFLD-1 patients will likely be referred back to primary care for treatment and expresses her confidence that resmetirom might be a good option for PCPs when treating these patients. The rest of the season focused on issues of biomarker inaccuracy. Jörn shares results from a presentation by Jerome Boursier on the accuracy of FIB-4 in Type 2 Diabetes patients and an analysis of the MAESTRO NAFLD-1 data he presented. In his presentation, 26% of patients with NAS >= 4 and biopsy-confirmed F2 or F3 NASH had normal ALT scores, and 80% had ALTs less than 2x normal. In Germany, where ALT is the test PCPs conduct before referring patients, Jörn expressed concerns about how many patients needing treatment are missed due to false ALT negatives. The rest of the discussion centers around defining the proper use of FIB-4 and areas with vast potential for misuse.
The International Liver Congress (#ILC2022) is the first major hepatology Congress to be held in person since the start of the pandemic (smaller, but very valuable, meetings like NASH-TAG, LiverCONNECT and Paris HASH have taken place with an in-person component, but the International Liver Congress and The Liver Meeting have not).The conversation takes place against the schedule of a live Congress on the day that focused on drug development. This presented scheduling challenges, which Louise Campbell addressed by combining two shorter conversations.The first conversation included Jörn Schattenberg, Mazen Noureddin and Ian Rowe and focused on a morning session titled "NAFLD: Diagnostics and non-invasive assessment." This conversation focused on several elements of this session: papers demonstrating the relative lessons and values of FAST, MAST and MEFIB, an analysis from the LITMUS Metacohort identifying the combination of metrics that did the best jobs of specifically predicting fibrosis, steatosis, ballooning and inflammation, and papers looking at the ability of FIB-4 to identify at-risk patients. The most important conclusions: (i) the LITMUS presentation attempted to correlate to biopsy, which is a suboptimal target; researchers should consider the limitations of biopsy in planning future trials; and (ii) many tests have significant value as long as we use them properly with an appreciation of what the test seeks to determine and why for that purpose, one test might be better or weaker than others.As this conversation winds down, Louise Campbell discusses interpretive challenges caused by the fact that studies do not list the generations of technology researchers use. She points out specifically that successive generations of FibroScan demonstrate significant differences in terms of tools that are available and the reliability of different tools. Finally, Jörn discusses a study in the Public Health session from the SEAL program suggesting that roughly half the patients never return for their second visits. After this, Mazen asks Jörn to discuss his presentation in the NAFLD Diagnostics session. Jörn presented results of a MAESTRO-NASH analysis in which the researchers assessed the ability of FIB-4 to identify and diagnose at-risk F2 and F3 patients from among a 2,000 patient cohort. Key point: 37% of patients in this trial had normal ALT and 80% had
Next week, >10,000 Fatty Liver stakeholders are expected to journey to London (rail strike and all) for the International Liver Congress (#ILC2022), the first meeting at this level since the pandemic started to include an in-person attendance option. This week, NASH Tsunami identifies some of the most important and intriguing non-embargoed presentations at #ILC2022. This conversation explores two of these: OS097, Machine learning algorithms identify novel biomarker combinations for NAFLD, from Jenny Lee (Netherlands); and FRI094, Clinical and economic evaluation of community-based preventative screening strategies for NAFLD in people with Type-2 diabetes melllitus, from Roberta Forlano (UK).Jörn Schattenberg selected OS097 as the first paper for the Surfers to discuss due to its robust dataset (720 liver-biopsied patients recruited prospectively at centers across Europe; 53% with NASH, 26% with advanced fibrosis and 7% with cirrhosis.) and intriguing task (identify the most robust biomarkers for predicting levels of steatosis, ballooning, inflammation and fibrosis independently). The AUCs for fibrosis were robust (0.90 in the test group and 0.84 in the validation set), while the AUCs for the steatosis measures were weaker (0.79 and 0.74, respectively.) Jörn notes that the histological markers vary between the four targets, with steatosis and ballooning predicted most strongly by BMI, inflammation by hemoglobin and fibrosis by VCTE. After questions, Jörn goes on to note that the CK-18 M 30 emerges as a predictor for both steatosis and fibrosis.The key question comes from Stephen, who asks how diabetes came into this equation in terms of metric, severity and length of disease. Jörn states that the only diabetes metric in the set was A1c, which was the 5th strongest for fibrosis. He also notes that length of disease is exceptionally challenging to determine in a study that relies on patient self-reports.Louise Campbell responds next, selecting FRI094, a clinical and economic assessment of community-based screening of Type 2 diabetes mellitus patients for Fatty Liver disease. This study began at Imperial while Louise still worked there. The study reported 17% of NAFLD patients with "significant" fibrosis (kPa>8.1 by VCTE), 11% had advanced fibrosis and 3% had cirrhosis (defined as kPa >12,1 by VCTE.) Any of these patients might have been defined by clinical, radiological or histological means.After questions, Louise would go on to note that all approaches were determine to be cost effective against a metric of 20,000 English pounds.Again, the pivotal question came from Stephen, who suggested that a kPa of 12.1 (the definition of cirrhosis here) would fit half of his practice. He used this point to remind listeners of the poor positive predictive value of VCTE as a single measure.When Stephen and Louise finish this point, Louise notes the positive recommendation on cost-effectivesness of community screening while acknowledging the issue around scoring of cirrhosis. Jörn then closes the discussion of this paper (and the conversation) by agreeing with Stephen's comment on the VCTE kPa and cirrhosis, but noting that the high levels indicate a serious challenge (even if not a level of cirrhosis).
Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. For the #NASHDay Wrap-up Panel, Global Liver Institute invited NASH Tsunami co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to join NASH Programs Director Jeff McIntyre to discuss themes of the day and major issues in the Fatty Liver community.This conversation includes the last fifteen minutes of the GLI NASH Day wrap-up panel. Jeff McIntyre asks two questions to the group. First, he asks each panelist to respond to the slogan “#StopNASHNow and its implication that for patients, it might be enough simply to arrest the progression of fibrosis, and therefore we should devote some of our research and regulatory energy to stopping the progression instead of focusing entirely on regression. For his last substantive question, he asks each of us to discuss something that puts a twinkle in our eyes as we consider the next 3-5 years of progress in the fight against Fatty Liver disease. Great questions that yield interesting and diverse answers from the three Surfers.
Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to celebrate the event and comment on one crucial trend or event most signified what the last year has meant in the Fatty Liver community.This conversation includes three sections:• First, Roger discusses the Law of Unintended Consequences in the context of the FDA Complete Response Letter to Intercept Pharmaceuticals over obeticholic acid, an event that many feared would bring all momentum around Fatty Liver disease to a standstill but, two years later, has driven real bursts of creative energy and innovative problem solving centered around the disease rather than a drug.• Second, Stephen's and Jörn's impassioned statements that the providers will never give up on addressing the challenges of NASH, both because, as Stephen describes, it is not in their character and because, as Jörn describes, “this disease is not going away.” As long as people are dying too young from the effects of NASH and HCC, he contends, the fight will continue.• Finally, Roger asked the panelists for bold predictions about what will have changed before we come together a year from now to celebrate the 6th International NASH Day.
Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. For the #NASHDay Wrap-up Panel, Global Liver Institute invited NASH Tsunami co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to join NASH Programs Director Jeff McIntyre to discuss themes of the day and major issues in the Fatty Liver community.This conversation includes highlights from the first 20 minutes of the GLI NASH Day wrap-up panel. It includes Jeff McIntyre's first two questions to the panel and responses from Jörn Schattenberg, Louise Campbell and me. Jeff's first question was about the role and relevance of International NASH Day in 2022, and his second question was about the areas where we need patient voice to make a difference today. Not surprisingly, the three Surfers gave answers to both questions that covered different issues but complemented each other nicely.
Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to celebrate the event and comment on one crucial trend or event most signified what the last year has meant in the Fatty Liver community.This conversation consists mostly of reactions from Jörn Schattenberg, Louise Campbell and Roger Green to Stephen's initial statement, followed by other thoughts from Stephen. The other Surfers are all impressed by the trial design. In response to a comment from Roger, Stephen comments enthusiastically on the unprecedented collaboration between sponsors, academics, regulators – the entire range of stakeholders – to resolve this issue. He goes on to note other questions – for example, the name of the disease – where the community is demonstrating unparalleled collaboration. All of this, he says, is leading to a proliferation of new research so vast that no one can keep up with all of it. There are three more points in this conversation:• Jörn raises Quentin Anstee's comments from Episode 26 that we need to develop a standard set of NITs to use in the evaluation process as another area where collaboration will be key• Stephen points out that we may see our first drug approval in 2023, which will add new levels of energy and resourcing to the development and education processes• Jörn begins to discuss his issue, which is the convergence between conferences to cover a range of issues that look past simple drug development to improve key questions from drug evaluation to clinical care pathways and inter-specialty collaboration to treat patients
Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to celebrate the event and comment on one crucial trend or event most signified what the last year has meant in the Fatty Liver community.This conversation is about collaboration. It starts with Jörn Schattenberg noting the increasing momentum for groups to work together and proceeds to explore two observations from Louise Campbell:• One about the rapidly expanding rate of change in the development of key products with particular emphasis on NITs• A second on the increasing momentum behind broad approaches to the NAFLD pandemic, including the expansion of patient advocacy organizations around the world to the increasing energy all the various stakeholders and medical specialties to collaborate in an integrated attack on NAFLD and NASH. She notes that this energy needs to translate to a global set of local conversations sensitive to how healthcare operates in countries and regions.From there, Jörn notes how Louise's prior work in Hepatitis C gives her an experience the NASH physicians will not have and Stephen lists big items with tremendous progress, momentum and potential to a crescendo.